Imaging agents

Abstract

The present invention provides novel amino acid compounds useful in detecting and evaluating brain and body tumors. These compounds have the advantageous properties of rapid uptake and prolonged retention in tumors and can be labeled with halogen isotopes such as fluorine-18, iodine-123, iodine-124, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77, bromine-82, astatine-210, astatine-211, and other astatine isotopes. These compounds can also be labeled with technetium and rhenium isotopes using known chelation complexes. The compounds disclosed herein bind tumor tissues in vivo with high specificity and selectivity when administered to a subject. Preferred compounds show a target to non-target ratio of at least 2:1, are stable in vivo and substantially localized to target within 1 hour after administration. Preferred compounds include 1-amino-2-[ 18 F]fluorocyclobutyl-1-carboxylic acid (2-[ 18 F]FACBC) and 1-amino-2-[ 18 ]fluoromethylcyclobutyl-1-carboxylic acid (2-[ 18 F]FMACBC). The labeled amino acid compounds of the invention are useful as imaging agents in detecting and/or monitoring tumors in a subject by PET or SPECT.

We claim: 
     
       1. A compound of the following formula, 
       
         
           
           
               
               
           
         
         or salt thereof, wherein 
         Y is (CR 5 R 6 ) n , N, O, S, Se; 
         n is 1-4; 
         R 4 , R 5  and R 6  are independently H, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, heteroaryl, aryl, haloaryl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, or halo; 
         R 1  is H, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, cycloalkenyl, halocycloalkenyl, cycloalkynyl, halocycloalkynyl, acyl, haloacyl, aryl, haloaryl, heteroaryl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, or bis(4-methoxyphenyl)methyl, 
         R 3  is H, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, cycloalkenyl, halocycloalkenyl, cycloalkynyl, halocycloalkynyl, acyl, haloacyl, aryl, haloaryl, heteroaryl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl. 
       
     
     
       2. The compound of  claim 1 , wherein halo is a non-radioactive F, Cl, Br, or I. 
     
     
       3. The compound of  claim 1 , wherein (CR 5 R 6 ) n is CH 2 . 
     
     
       4. The compound of  claim 1 , wherein R 4  is hydrogen. 
     
     
       5. The compound of  claim 1 , wherein R 3  is t-butyl. 
     
     
       6. The compound of  claim 1 , wherein R 1  is acyl. 
     
     
       7. The compound of  claim 6 , wherein acyl is t-butoxycarbonyl. 
     
     
       8. A compound di-tert-butyl 2-oxa-3-thia-4-azabicyclo[3.2.0]heptane-4,5-dicarboxylate 3,3-dioxide. 
     
     
       9. A kit comprising a compound of  claim 1  and a halogen, astatine, technetium, or rhenium radio isotope labeling reagent. 
     
     
       10. The kit of  claim 9  wherein the compound is di-tert-butyl 2-oxa-3-thia-4-azabicyclo[3.2.0]heptane-4,5-dicarboxylate 3,3-dioxide. 
     
     
       11. The kit of  claim 9 , wherein the radio isotope labeling reagent is salt of  18 F.